The public health utility of genome-wide association study results for smoking behavior

New approaches to improve smoking cessation rates are needed. In recent years, substantial progress has been made in understanding the genetics of smoking behavior, and this knowledge may eventually be used to personalize treatment for smokers. Although there are highly significant and reproducible genetic associations, none are yet ready for clinical applications. We suggest that translational research from several disciplines, including behavioral science, ethics and economics, should be performed in parallel with ongoing genome-wide association studies for smoking behavior and pharmacogenetic trials. The coordinated effort of multidisciplinary research teams will help reveal the circumstances under which we can translate genetic insights into clinical practice in the hope of reducing the burden of smoking in society

Cigarettes and oral snuff use in Sweden: prevalence and transitions

To investigate the prevalence and patterns of transitions between cigarette and snus use

The prevalence of self-reported chronic fatigue in a U.S. twin registry

To investigate the prevalence and correlates of various definitions of self-reported lifetime fatiguing illness in a U.S. twin registry

A searchable database of genetic evidence for psychiatric disorders

This paper describes a new bioinformatic tool for use in psychiatric research, “SLEP” (Sullivan Lab Evidence Project). SLEP is a searchable archive of findings from psychiatric genetics that is freely available on the web for non-commercial use (http://slep.unc.edu). Via a simple interface, users can retrieve findings from genomewide linkage, genomewide association, and microarray studies for ADHD, autism, bipolar disorder, eating disorders, major depression, nicotine dependence, and schizophrenia. Findings can be save to disk or viewed via a genome browser

Feeling Bad in More Ways than One: Comorbidity Patterns of Medically Unexplained and Psychiatric Conditions

Considerable overlap in symptoms and disease comorbidity has been noted among medically unexplained and psychiatric conditions seen in the primary care setting, such as chronic fatigue syndrome, low back pain, irritable bowel syndrome, chronic tension headache, fibromyalgia, temporomandibular joint disorder, major depression, panic attacks, and posttraumatic stress disorder

The STAGE cohort: A prospective study of tobacco use among Swedish twins

We investigated patterns of cigarette smoking and Swedish snus (oral smokeless tobacco) use in a population-based sample of 19,073 Swedish twins 20–47 years old who participated in the baseline assessment of a prospective study of tobacco use and cessation in 2005–2006. Age-adjusted prevalence odds ratios (POR) and 95% confidence intervals (CI ) describe the association between tobacco use and sex, after adjustment for non-independence of twin pairs. Kaplan-Meier survival methods produced cumulative incidence curves of age at initiation of tobacco use. Slightly more than half of the baseline population was female (55.2%); the mean age at interview was 33.3 (±7.2) years and did not differ by sex. Having ever smoked daily was less common among males than females (11.9% vs. 15.3%; POR=0.70 [0.64–0.77]), while having ever used snus daily was more common among males than females (31.1% vs. 4.8%; POR 11.7 [95% CI=10.6–13.1]). The median age at initiation of smoking was 15 years for both sexes; median age at onset of snus use was 15 years for males and 18 years for females. Nicotine dependence scores were higher for males than females, and for current than former smokers. Findings from this study are in contrast to our previously published report on tobacco use among 32,123 Swedish twins 42–64 years old who completed a similar survey, and reported lower rates of snus use at later ages. Patterns of tobacco use may be changing in Sweden; snus use appears to be increasing, while daily smoking appears to be decreasing in popularity among the younger Swedish twins

Initial Reactions to Tobacco Use and Risk of Future Regular Use

Introduction: Studies suggest that initial smoking pleasure influences future smoking behavior. We investigated how initial reactions to cigarettes or Swedish smokeless tobacco (snus) were associated with future use among 10,708 adults from the Swedish Twin Registry

Genomewide linkage survey of nicotine dependence phenotypes

A comprehensive understanding of the etiology and neurobiology of nicotine dependence is not available. We sought to identify genomic regions that might contain etiologically-relevant loci using genomewide univariate and bivariate linkage analyses

All SNPs Are Not Created Equal: Genome-Wide Association Studies Reveal a Consistent Pattern of Enrichment among Functionally Annotated SNPs

Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1−FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci

Smoking and Genetic Risk Variation Across Populations of E uropean, A sian, and A frican A merican Ancestry—A Meta‐Analysis of Chromosome 15q25

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91126/1/gepi21627.pd